This proposal is a resubmission of a previous grant (AM 28420-04) which was reviewed in June, 1986. This proposal deals with the metabolism and effects of vitamin D metabolites on isolated bone cells. The specific aims have been refocused 1) to elucidate the role of age on the extra renal metabolism of 25-hydroxy-vitamin D (25(OH)D3) by bone cells, 2) to study the effect of exogenous stimulators of proliferation and differentiation on the metabolism of 25(OH)D3, 3) to refine a cell isolation technique to the point of identifying which bone cell phenotype is responsible for the metabolism of 25(OH)D3 and 4) to purify and study the effect of hormones on bone cell phosphotyrosine phosphatase (PTPase). The long term objectives of this work are to determine whether extra renal metabolism of vitamin D metabolites by bone cells is physiologically important. Moreover, this work will also explore the role of calcitropic hormones in regulating cell proliferation by their action on the newly discovered enzyme, PTPase. Since the previous submission of this proposal new information regarding the regulation of a chick bone cell 25(OH)D3-1- hydroxylase has been obtained. This enzyme appears to be regulated in a complex way by vitamin D metabolites and has been shown to have a short half-life (approximately 5 hours).